Schizophrenia is a chronic psychiatric disorder, characterized by a wide spectrum of psychopathology, including positive symptoms such as aberrant or distorted mental representations (e.g., hallucinations, delusions), negative symptoms characterized by diminution of motivation and adaptive goal-directed action (e.g., anhedonia, affective flattening, avolition), and cognitive impairment. While abnormalities in the brain are proposed to underlie the full spectrum of psychopathology in schizophrenia, currently available antipsychotics are largely ineffective in treating cognitive impairments in schizophrenia patients.
Cognitive impairments in schizophrenia involve both frontal and temporal lobe functions that include memory, attention, processing speed, and executive control. Recent observations, drawn from preclinical animal models and human neuroimaging studies, indicate that altered brain activity/excitability in the medial temporal lobe memory system may contribute to cognitive impairment and may also play a role in augmenting psychotic symptoms due to disinhibition of dopaminergic neurons.
Cognitive deficits are increasingly recognized as a key clinical feature that can be detected in a prodromal phase and in remission, as well as during full expression of the illness but are not effectively treated by available antipsychotics. Because untreated features of schizophrenia, especially impaired cognition, predict long-term disability in patients (Green et al., Schizophr. Res. 2004, 72, 41-45), it is critical to develop effective therapies for the spectrum of this illness.